The overall objective of the total project is to determine the underlying mechanisms of sex-linked anemia (gene symbol, sla), microcytic anemia (gene symbol, mk), the anemia of the Belgrade laboratory rat (gene symbol, b), and the mottled trait (gene symbol, Mo) as a means of identifying and analyzing single, genetically controlled steps in mammalian iron, copper and globin metabolism. The delivery of iron to the b/b reticulocyte will be examined by incubation with doubly labelled (59Fe, 125I) transferrin of various iron saturations at 37 degrees centigrade and 4 degrees centigrade. The interrelationships of reticulocyte iron delivery and globin synthesis will be investigated by measuring b/b and ion/ion globin synthesis in a wheat germ cell free system in the presence and absence of exogenous hemin. The defect in copper metabolism in the mottled trait will be studied examining the uptake and release of 64Cu by cultured fibroblasts and the subcellular distribution of accumulated copper.